Molecular evidence on the protective effect of ellagic acid on phosalone-induced senescence in rat embryonic fibroblast cells. (February 2017)

• Record Type: Journal Article
• Authors: Baeeri, Maryam; Momtaz, Saeideh; Navaei-Nigjeh, Mona; Niaz, Kamal; Rahimifard, Mahban; Ghasemi-Niri, Seyedeh Farnaz; Sanadgol, Nima; Hodjat, Mahshid; Sharifzadeh, Mohammad; Abdollahi, Mohammad
• Is Part Of: Food and chemical toxicology. Volume 100(2017)
• Page Start: 8
• Page End: 23
• Publication Date: 2017-02
• Subjects: Aging -- Cell cycle -- Ellagic acid -- Inflammatory cytokines -- Oxidative stress -- Phosalone -- Senescence; ABC avidin-biotin-peroxidase complex -- ATM ataxia-telangiectasia mutated -- ATP adenosine triphosphate -- ATR ATM- and Rad3-Related -- BCA bicinchoninic acid -- CDKN1A cyclin-dependent kinase inhibitor p21 -- Ct cycle number -- DCFH-DA 2′, 7′-dichlorofluorescin diacetate -- DMEM dulbecco's modified eagle's medium -- DMSO dimethyl sulfoxide -- DNA deoxyribonucleic acid -- DNA-PK DNA-dependent protein kinase -- DTT DL-dithiothreitol -- EA ellagic acid -- EDTA ethylene diamine tetra acetic acid -- US EPA United States Environment Protection Agency -- FBS fetal bovine serum -- FDA food and drug administration -- FRAP ferric reducing antioxidant power -- GAPDH glyceraldehyde 3-phosphate dehydrogenase -- HCl hydrochloric acid -- HRP horseradish peroxidase -- IC50 inhibitory concentration -- IL-1β interleukine-1β -- IL-6 interleukine-6 -- LD50 lethal dose -- LPO lipid peroxidation -- MDA malondialdehyde -- MTT 3-4, 5 dimethylthiazol-2-yl-2, 5-diphenyltetrazolium bromide -- NF-κB nuclear factor-kappa-B -- OPs organophosphorus -- OSRDs oxidative stress related diseases -- PBS phosphate-buffered saline -- PI propidium iodide -- PLN phosalone -- p38 p38 mitogen activated protein kinases -- PRAK p38-regulated/activated protein kinase -- PS phosphatidylserine -- PVDF polyvinylidene fluoride -- RB retinoblastoma -- REF rat embryonic fibroblast -- ROS reactive oxygen species -- RT-PCR real time-reverse transcription polymerase chain reaction -- SASPP senescence-associated-secretoryphenotype proteins -- SA-β-GAL senescence associated β-galactosidase -- SDS-PAGE sodium dodecyl sulfate polyacrylamide gel electrophoresis -- TAP total antioxidant power -- TBA thiobarbituric acid -- TBARS thiobarbituric acid reactive substances -- TBS tris-buffered saline -- TGF-β transforming growth factor-beta -- TMB 3, 3′, 5, 5′-tetramethylbenzidine -- TNF-α tumor necrosis factor-alpha -- TP53 Tumor protein -- TPTZ tri (2-pyridyl)-s-triazine -- TTM total thiol molecules -- TUMS Tehran University of Medical Sciences -- X-gal 5-bromo-4-chloro-3-indolyl-β-d-galactopyranoside -- WHO word health organization; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2016.12.008
• Languages: English
• ISSNs: 0278-6915

Abstract

Abstract: Salient evidence testifies the link between organophosphorus (OPs) exposure and the formation of free radical oxidants; and it is well accepted that free radicals are one of the basic concerns of senescence. To show the oxidative features of phosalone (PLN) as a key member of OPs, to induce senescence in rat embryonic fibroblast (REF) cells and to demonstrate the beneficial effects of the known antioxidant ellagic acid (EA) in diminishing the PLN-induced toxic effects, the levels of cell viability, oxidative stress markers, inflammatory cytokines, telomerase activity, and the expression of the genes related to senescence were investigated. Our results lend support to the hypothesis that PLN enhances the entire premature senescence parameters of REF cells. This accounts for the mechanistic approval of the role of OPs in induction of senescence in rat fibroblasts. Moreover, incorporation of EA diminished PLN toxicity mainly through suppression of p38 and p53 at gene and protein levels, and tempered the inflammation factors (TNF-α, IL-1β, IL-6 and NF-κB), which further affected cell division. Analysis of cell cycle showed that the percentage of G0/G1 arrest, in REF cells treated by EA was elevated as compared to control and PLN treated cells. Graphical abstract: Highlights: PLN enhanced the oxidative stress, inflammatory response, and disrupted cell division. EA dose-dependently deactivated PLN-induced senescence in REFs. EA depressed PLN toxicity through repression of P38 and P53 at the gene and protein levels. EA promoted expression of telomerase in REFs of PLN-induced senescence.